SELEX, i.e., Systematic Evolution of Ligands by Exponential Enrichment, is a process of isolating oligonucleotide ligands of a chosen target molecule (see Tuerk and Gold, Science 249:505-510, (1990), U.S. Pat. Nos. 5,475,096, 5,595,877, and 5,660,985). SELEX as described in Tuerk and Gold involves admixing the target molecule with a pool of oligonucleotides (e.g., RNA) of diverse sequences; retaining complexes formed between the target and oligonucleotides; recovering the oligonucleotides bound to the target; reverse-transcribing the RNA into DNA; amplifying the DNA with polymerase chain reactions (PCR); transcribing the amplified DNA into RNA; and repeating the cycle with ever increasing binding stringency. Three enzymatic reactions are required for each cycle. It usually takes many cycles (e.g., between 12-15 cycles) to isolate aptamers of high affinity and specificity to the target. An aptamer is an oligonucleotide that is capable of binding to an intended target substance but not other molecules under the same conditions.
Bock et al., (1990) Nature 355:564-566, describes another approach of isolating aptamers. Bock's process is different from that of Tuerk and Gold in that only one enzymatic reaction is required for each cycle (i.e., PCR) because the nucleic acid library in Bock's method is comprised of DNA instead of RNA. The identification and isolation of aptamers of high specificity and affinity with the method of Bock et al. still requires repeated cycles in a chromatographic column.
Conrad et al., (1996) Methods in Enzymol. 267:336-367, describes a variety of methods for isolating aptamers, all of which employ repeated cycles to enrich target-bound ligands and require a large amount of purified target molecules.